Use of a Short-Acting β1 Blocker During Endotoxemia May Reduce Cerebral Tissue Oxygenation if Hemodynamics are Depressed by a Decrease in Heart Rate

Abstract

Background: A decrease in heart rate (HR) using a short-acting β blocker has potential benefits in sepsis; however, depression of hemodynamics and reduction of cerebral oxygenation may also occur in endotoxemia.

Methods: Seventeen swine were allocated to landiolol or control groups. In the landiolol group, the dose was sequentially changed from 0 to 40 to 200 μg kg min, and stopped. Hemodynamics, blood variables, and the cerebral tissue oxygenation index (TOI) were recorded by near infrared spectroscopy at each dose. Lipopolysaccharide (LPS) was then administered continuously at 1 μg kg h after a 100 μg bolus administration. After 30 and 150 min, as two severity stages of endotoxemia (endotoxemia 1 and 2), landiolol was administered as above and measurements were made. In the control group, landiolol was not administered, but measurements were made.

Results: LPS increased HR and landiolol decreased HR, with similar effects in each endotoxemia stage. In endotoxemia 1, LPS decreased stroke volume (SV), but landiolol restored SV to a value similar to that before endotoxemia, and did not decrease cardiac output (CO), even at 200 μg kg min. In contrast, landiolol did not restore SV in endotoxemia 2, resulting in a decrease in CO and mean arterial pressure, accompanied with a dose-dependent decrease in TOI.

Conclusions: A short-acting β blocker has various hemodynamic effects in endotoxemia. Use of a short-acting β blocker during endotoxemia may reduce cerebral tissue oxygenation if hemodynamics are depressed by a decrease in HR.